Search

Background: While Streptococcus agalactiae (Group B Streptococcus [GBS]) infections in infants usually result from maternal transmission, healthcare-associated cases, particularly in the neonatal intensive care unit (NICU), can occur. Whole genome sequencing (WGS) can aid in investigating GBS outbreaks among infants in hospital settings. The aim of the study is to describe the investigation of GBS infections in NICU using WGS. Methods: Infection prevention and control (IPAC) at our hospital monitors the occurrence of late-onset GBS disease (LOD) in our 57-bed NICU, which consists of all private rooms. The occurrence of 2 cases of LOD within 2 weeks triggered an investigation, including WGS of the two isolates and isolates causing invasive GBS during the last 6 months in the unit. GBS isolates underwent WGS using Illumina at Canada’s National Microbiology Laboratory. All affected patients underwent chart-review. Outbreak description and investigation: In August 2023, two NICU neonates (patients 2,3) experienced LOD two weeks apart, one with bacteremic meningitis and the other with two bacteremic episodes three weeks apart. While WGS was pending two additional cases of late-onset GBS bacteremia (patients 4,5) occurred. Isolates from Pts 2,3 and 5 were indistinguishable from each other and from an isolate from an infant admitted to the NICU with early onset bacteremia on July 27, 2023 (day 1 of life) (patient 1). Weekly point prevalence for throat and rectal colonization over 3 weeks identified five infants colonized with unrelated strains. An additional long-stay infant (patient 6) developed GBS conjunctivitis due to a strain indistinguishable from (patient 4) by pulse field gel electrophoresis, WGS for the second cluster is pending. IPAC interventions: Lapses in IPAC practices were observed, with no commonalities among cases other than similar geographic location within the unit. We hypothesized transmission was due to horizontal transmission between babies due to these lapses. Basic IPAC measures, including hand hygiene and environmental cleaning, were reinforced; Additional Precautions were not used due to private rooms’ unit structure. No environmental samples were taken due to lack of an obvious environmental point or common source. Point prevalence monitoring persisted until no new cases related to the outbreak strains were further identified in three consecutive weekly point prevalence. Conclusions: Increased awareness of healthcare-associated transmission is crucial in NICU as LOD GBS emerges. WGS plays a key role in identifying transmission. Detecting a multi-strain outbreak can appropriately redirect investigations. Legend: Figure 1: Timeline of stay at NICU and infection timing for patients 1-6

Background: The molecular and epidemiological landscape of C. difficile infection (CDI) has evolved markedly in the last decade; however, limited information is available contrasting differences between adult and pediatric populations. We describe a multicenter study evaluating healthcare-associated (HA) and community-associated (CA) adult and pediatric-CDI identified in the Canadian Nosocomial Infection Surveillance Program (CNISP) network from 2015 to 2022. Methods: Hospitalized patients with CDI were identified from up to 84 hospitals between 2015–2022 using standardized case definitions. Cases were confirmed by PCR, cultured, and further characterized using ribotyping and E-test. We used two-tailed tests for significance (p≤0.05). Results: Of 30,817 cases reported, 29,245 were adult cases [HA-CDI (73.2%), CA-CDI (26.8%)] and 1,572 were pediatric cases [HA-CDI (77.7%), CA-CDI (22.3%)]. From 2015 to 2022, HA-CDI rates decreased 19.7% (p=0.007) and 29.4% (p=0.004) in adult and pediatric populations, respectively (Figure 1). CA-CDI rates remained relatively stable in the adult population (p=0.797), while decreasing 60.7% in the pediatric population (p=0.013). Median ages of adult and pediatric patients were 70 (interquartile range (IQR), 58–80) and seven (IQR, 3–13) years, respectively. Thirty-day all-cause mortality was significantly higher among adult vs. Pediatric CDI patients (11.0% vs 1.4%, p < 0.0001). No significant differences in other severe outcomes were found. Ribotyping and susceptibility data were available for 4,620 samples: 3,558 adult (77.0%) and 1,062 pediatric (23.0%). The predominant adult and pediatric ribotypes (RT) were 106 (12.2/16.2%), 027 (11.4/3.2%), and 014 (8.8/8.2%). Overall, RT027 prevalence significantly decreased from 17.9% in 2015 to 3.2% in 2022 (p=0.003), while RT106 increased from 8.5% to 14.4%. Resistance rates among adult and pediatric isolates were similar for all antimicrobials tested except moxifloxacin (16.2% vs. 6.2%, p < 0.0001, respectively). Adult moxifloxacin resistance decreased from 30% to 6.3% from 2015 to 2022 (p=0.006). Adults with moxifloxacin-resistant CDI were older (median: 74 vs. 69 years, p < 0.001) and had higher thirty-day all-cause mortality (13% vs. 9.8%, p=0.041) and recurrence (10% vs. 5.7%, p < 0.001) compared to those with moxifloxacin non-resistant CDI, while these trends were not observed in pediatric patients. Among RT027 strains, moxifloxacin resistance decreased from 91.0% in 2015 to 7.1% in 2022. There was one metronidazole-resistant pediatric sample in 2018 and no resistance to vancomycin or tigecycline in either population. Conclusion: We have found differences in the epidemiological and molecular characteristics of adult and pediatric CDI, with higher thirty-day all-cause mortality among adults. Overall, RT106 has replaced RT027 as the predominant ribotype with a concomitant decrease in fluoroquinolone resistance.

Background: Serratia marcescens (S. marcescens) is an environmentally associated organism known for causing healthcare associated infections and outbreaks in neonatal intensive care units (NICUs). The colonization or infection rates in NICU settings remain uncertain. This study aims to evaluate the rate of baseline colonization and clinical infection and relatedness of S. marcescens isolates. Methods: Prospective surveillance of rectal colonization and clinical infection of S. marcescens was conducted on patients admitted to the NICU at Mount Sinai Hospital in Toronto, Ontario, from March 1, 2023, to September 30, 2023. The NICU is a 57 bed unit with all private rooms. Monthly point prevalence assessments by rectal screening were performed, alongside active surveillance for clinical infections associated with S. marcesens. Isolates from screening or clinical samples underwent assessment for relatedness using pulse field gel electrophoresis (PFGE). Results: Over the 7 month study period, 12 different patients (5.4%) were colonized/infected with S. marcescens. Among these, 10 patients (4.5%) were identified through rectal screening (316 rectal swabs were collected from 224 patients) and two patients (0.9%) exhibited positive clinical specimens (urine and endotracheal aspirate) in association with pyelonephritis and ventilator-associated pneumonia, respectively. Of the two clinical cases, one case showed a negative preceding rectal swab and the other detected through a clinical sample before the point prevalence date. The age at which a positive S. marcescens swab or positive clinical specimen was identified ranged from 4 to 66 days (median=18 days, IQR 5-38.8) (Figure 1). Sixty seven infants had repeated screening. Three out of 67 (4.5%) were colonized with S. marcescens, the timing and sequence of positive and negative testing are presented in Figure 2. Females demonstrated a higher positivity rate compared to males [9.1% (9/99) vs 2.4% (3/125), p=0.04, respectively]. PFGE analysis of all 12 (100%) isolates revealed a polyclonal pattern. Most cases were detected from March to May in 9/12 cases (75%). Ten different strains were identified. Notably, two strains demonstrated clusters of two cases each, one during March and the other during May (Figure 3). No mortality was reported among the cases. Conclusions: The study highlights the polyclonal nature of S. marcesens and raises questions about the utility of point prevalence in anticipating clinical cases or patient-to-patient transmission, especially in patients with clinical infection where there were no preceding positive screening tests.

Abstract Background Previous research suggests that moral distress contributes to burnout in nurses and other healthcare workers. We hypothesized that burnout both contributed to moral distress and was amplified by moral distress for hospital workers in the COVID-19 pandemic. This study also aimed to test if moral distress was related to considering leaving one’s job. Methods A cohort of 213 hospital workers completed quarterly surveys at six time-points over fifteen months that included validated measures of three dimensions of professional burnout and moral distress. Moral distress was categorized as minimal, medium, or high. Analyses using linear and ordinal regression models tested the association between burnout and other variables at Time 1 (T1), moral distress at Time 3 (T3), and burnout and considering leaving one’s job at Time 6 (T6). Results Moral distress was highest in nurses. Job type (nurse (co-efficient 1.99, p

Abstract Background The term resilience is used to refer to multiple related phenomena, including: (i) characteristics that promote adaptation to stressful circumstances, (ii) withstanding stress, and (iii) bouncing back quickly. There is little evidence to understand how these components of resilience are related to one another. Skills-based adaptive characteristics that can respond to training (as opposed to personality traits) have been proposed to include living authentically, finding work that aligns with purpose and values, maintaining perspective in the face of adversity, managing stress, interacting cooperatively, staying healthy, and building supportive networks. While these characteristics can be measured at a single time-point, observing responses to stress (withstanding and bouncing back) require multiple, longitudinal observations. This study’s aim is to determine the relationship between these three aspects of resilience in hospital workers during the prolonged, severe stress of the COVID-19 pandemic. Methods We conducted a longitudinal survey of a cohort of 538 hospital workers at seven time-points between the fall of 2020 and the spring of 2022. The survey included a baseline measurement of skills-based adaptive characteristics and repeated measures of adverse outcomes (burnout, psychological distress, and posttraumatic symptoms). Mixed effects linear regression assessed the relationship between baseline adaptive characteristics and the subsequent course of adverse outcomes. Results The results showed significant main effects of adaptive characteristics and of time on each adverse outcome (all p

Introduction Informed consent forms (ICFs) for randomised clinical trials (RCTs) can be onerous and lengthy. The process has the potential to overwhelm patients with information, leading them to miss elements of the study that are critical for an informed decision. Specifically, overly long and complicated ICFs have the potential to increase barriers to trial participation for patients with mild cognitive impairment, those who do not speak English as a first language or among those with lower medical literacy. In turn, this can influence trial recruitment, completion and external validity.Methods and analysis SIMPLY-SNAP is a pragmatic, multicentre, open-label, two-arm parallel-group superiority RCT, nested within a larger trial, the Staphylococcus aureus Network Adaptive Platform (SNAP) trial. We will randomise potentially eligible participants of the SNAP trial 1:1 to a full-length ICF or a SIMPlified LaYered (SIMPLY) consent process where basic information is summarised with embedded hyperlinks to supplemental information and videos. The primary outcome is recruitment into the SNAP trial. Secondary outcomes include patient understanding of the clinical trial, patient and research staff satisfaction with the consent process, and time taken for consent. As an exploratory outcome, we will also compare measures of diversity (eg, gender, ethnicity), according to the consent process randomised to. The planned sample size will be 346 participants.Ethics and dissemination The study has been approved by the ethics review board (Sunnybrook Health Sciences Research Ethics Board) at sites in Ontario. We will disseminate study results via the SNAP trial group and other collaborating clinical trial networks.Trial registration number ClinicalTrials.gov Registry (NCT06168474; www.clinicaltrials.gov).

Background Residents in long-term care homes, who tend to be of advanced age and frail, are at increased risk of respiratory infections. The respiratory microbiota is known to change with age, but whether these changes contribute to the risk of infection is not known. Our goal was to determine how the nasal microbiota of frail older adults changes during symptoms of influenza-like illness (ILI) and how this may be impacted by enrolment in a placebo-controlled trial testing the feasibility of administering a Lactobacillus rhamnosus GG probiotic to prevent respiratory infection (2014–2017). Methods The microbiome of the nasal (mid-turbinate) of 150 residents of long-term care homes was interrogated using 16S rRNA gene sequencing. Results We identified a diverse and individualised microbiota which could be separated into nine distinct clusters based on Bray–Curtis distances. Samples collected during symptoms of ILI differed statistically from those collected pre- and post-cold and influenza season, and we observed decreased temporal stability (as measured by movement between clusters) in individuals who experienced ILI compared to those who did not. Conclusions The use of probiotics decreased ILI-induced changes to the microbiota; however, it is not clear whether this decrease is sufficient to prevent respiratory illness.

Background: Data regarding the effects of the SARS-COV-2 (COVID-19) pandemic on healthcare-associated infections (HAIs) in Canadian acute-care hospitals are limited. We examined the impact of the COVID-19 pandemic on HAIs and antimicrobial resistant organisms in hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Methods: We analyzed 13,406 HAIs including adult mixed intensive care unit (ICU) central-line–associated bloodstream infections (CLABSIs), and healthcare-associated (HA) Clostridioides difficile infection (CDI), methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI), vancomycin-resistant Enterococcus (VRE) BSI, and carbapenemase-producing Enterobacterales (CPE) infections collected using standardized case definitions and questionnaires from 29–64 hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) from January 2018 to December 2021. We used a generalized linear mixed model with quasi-Poisson distribution to assess step and slope changes in monthly HAI rates between the pre–COVID-19 pandemic period (January 1, 2018–February 29, 2020; 26 time points) and the COVID-19 pandemic period (March 1, 2020–December 31, 2021; 22 time points). Results were reported as incidence rate ratios (IRRs) with 95% confidence intervals (CIs) and adjusted for seasonality, hospital clustering, and hospital characteristics of interest. Results: In the CNISP network, 7,352 (55%) HAIs were reported in the prepandemic period and 6,054 (45%) in the pandemic period. Median age was significantly younger during the pandemic period compared to the prepandemic period among patients with HA-CDI, HA-MRSA BSI, and adult mixed ICU CLABSIs, and more than half of cases among all reported HAIs were male (range, 52%–65%). The 30-day all-cause in-hospital mortality rate did not significantly change between the prepandemic and pandemic periods for all reported HAIs and was highest among HA-VRE BSIs (34%). Modeling results indicated that the COVID-19 pandemic was associated with an immediate increase in HA-CDI and adult mixed ICU CLABSI rates whereas HA-MRSA BSI, HA-CPE and HA-VRE BSI rates immediately decreased. However, pandemic status did not have a statistically significant lasting impact on monthly rate trends for all reported HAIs after adjusting for seasonality, clustering, and hospital covariates (Fig. 1 and 2). Adjusted IRRs for all HAIs ranged from 1.00 to 1.01 (95% CI, 0.94–0.99 to 1.01–1.05).

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p

Abstract Background The mental health effects of healthcare work during the COVID-19 pandemic have been substantial, but it is not known how long they will persist. This study aimed to determine if hospital workers’ burnout and psychological distress increased monotonically over 1 year, during which waves of case numbers and hospitalizations waxed and waned, or followed some other pattern. Methods A prospective longitudinal survey was conducted at four time-points over 1 year in a cohort of 538 hospital workers and learners, which included validated measures of burnout (emotional exhaustion scale of Maslach Burnout Inventory) and psychological distress (K6). Repeated measures ANOVA tested changes over time and differences between subjects by occupational role, age and ethnic group. The direction and magnitude of changes over time were investigated by plotting rates of high scores (using cut-offs) at each time-point compared to case rates of COVID-19 in the city in which the study took place. Results There were significant effects of occupational role (F = 11.2, p

Abstract Background The provision of care to pregnant persons and neonates must continue through pandemics. To maintain quality of care, while minimizing physical contact during the Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV2) pandemic, hospitals and international organizations issued recommendations on maternity and neonatal care delivery and restructuring of clinical and academic services. Early in the pandemic, recommendations relied on expert opinion, and offered a one-size-fits-all set of guidelines. Our aim was to examine these recommendations and provide the rationale and context to guide clinicians, administrators, educators, and researchers, on how to adapt maternity and neonatal services during the pandemic, regardless of jurisdiction. Method Our initial database search used Medical subject headings and free-text search terms related to coronavirus infections, pregnancy and neonatology, and summarized relevant recommendations from international society guidelines. Subsequent targeted searches to December 30, 2020, included relevant publications in general medical and obstetric journals, and updated society recommendations. Results We identified 846 titles and abstracts, of which 105 English-language publications fulfilled eligibility criteria and were included in our study. A multidisciplinary team representing clinicians from various disciplines, academics, administrators and training program directors critically appraised the literature to collate recommendations by multiple jurisdictions, including a quaternary care Canadian hospital, to provide context and rationale for viable options. Interpretation There are different schools of thought regarding effective practices in obstetric and neonatal services. Our critical review presents the rationale to effectively modify services, based on the phase of the pandemic, the prevalence of infection in the population, and resource availability.

Summary: Background: Global estimates suggest millions of deaths annually are associated with antimicrobial resistance (AMR) but these are generated from scarce data on the relative risk of death attributable to drug-resistant versus drug-sensitive infections. Methods: We examined all episodes of E. coli bloodstream infection in Ontario, Canada between 2017 and 2020, and measured 90 day mortality among those with resistant versus sensitive isolates for each of 8 commonly used antibiotic classes and a category of difficult to treat resistance (DTTR). We used multivariable logistic regression to calculate an adjusted odds of mortality associated with AMR, after accounting for patient demographics, comorbidities, and prior healthcare exposure. Findings: Among 14,548 eligible episodes of E. coli bloodstream infection, resistance was most common to aminopenicillins (46.8%), followed by first generation cephalosporins (38.8%), fluoroquinolones (26.5%), sulfonamides (24.1%), third generation cephalosporins (13.8%), aminoglycosides (11.7%), beta-lactam-beta-lactamase-inhibitors (9.1%) and carbapenems (0.2%). Only 18 (0.1%) episodes exhibited DTTR. For each antibiotic class, the unadjusted odds of mortality (OR) were higher among resistant isolates, but after accounting for patient characteristics the adjusted odds (aOR) of mortality were attenuated: aminopenicillins (OR 1.22, 95% CI 1.12–1.33; aOR 1.09, 95% CI 0.99–1.20), first generation cephalosporins (OR 1.24, 95% CI 1.14–1.35; aOR 1.07, 95% CI 0.97–1.18), third generation cephalosporins (OR 1.64, 95% CI 1.47–1.82; aOR 1.29, 95% CI 1.15–1.46), beta-lactam-beta-lactamase-inhibitors (OR 1.69, 95% CI 1.52–1.89, aOR 1.28, 95% CI 1.13–1.45), carbapenems (OR 3.11, 95% CI 1.52–6.34; aOR 2.06, 95% CI 0.91–4.66), sulfonamides (OR 1.19, 95% CI 1.07–1.31, aOR 1.06, 95% CI 0.95–1.18), fluoroquinolones (OR 1.49, 95% CI 1.36–1.64, aOR 1.16, 95% CI 1.05–1.29), aminoglycosides (OR 1.43, 95% CI 1.27–1.62; aOR 1.27, 95% CI 1.11–1.46), and DTTR (OR 3.71, 95% CI 1.46–9.41; aOR 2.58, 95% CI 0.87–7.66). Interpretation: AMR is associated with substantial increased mortality among patients with E. coli bloodstream infection, particularly for resistance to classes commonly used as empiric treatment. Surveillance for AMR-associated mortality should incorporate adjustment for patient characteristics and prior healthcare utilization. Funding: This work was supported by a project grant from CIHR (grant number 159503). This study was also supported by ICES, which is funded by an annual grant from Ontario Ministry of Health and Long-Term Care (MOHLTC).

OBJECTIVES:. Clinical research in Canada is conducted primarily in “academic” hospitals, whereas most clinical care is provided in “community” hospitals. The objective of this nested observational study was to compare patient characteristics, outcomes, process-of-care variables, and trial metrics for patients enrolled in a large randomized controlled trial who were admitted to academic and community hospitals in Canada. DESIGN:. We conducted a preplanned observational study nested within the Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT, a randomized controlled trial comparing probiotics to placebo in mechanically ventilated patients) Research Program. SETTING:. ICUs. PATIENTS:. Mechanically ventilated patients. MEASUREMENTS:. We compared patient characteristics, interventions, outcomes, and trial metrics between patients enrolled in PROSPECT from academic and community hospitals. MAIN RESULTS:. Participating centers included 34 (82.9%) academic and seven (17.1%) community hospitals, which enrolled 2,203 (86.2%) and 352 (13.8%) patients, respectively. Compared with academic hospitals, patients enrolled in community hospitals were older (mean [sd] 62.7 yr [14.9 yr] vs 59.5 yr [16.4 yr]; p = 0.044), had longer ICU stays (median [interquartile range {IQR}], 13 d [8–23 d] vs 11 d [7–8 d]; p = 0.012) and higher mortality (percentage, [95% CI] in the ICU, 30.4% [25.8–35.4%]vs 20.5% [18.9–11.3%]; p = 0.002) and hospital (40.6% [35.6–45.8%] vs 26.1% [24.3–27.9%]; p < 0.001). Trial metrics, including informed consent rate (85.9% vs 76.3%; p = 0.149), mean (sd) monthly enrolment rate (2.1 [1.4] vs 1.1 [0.7]; p = 0.119), and protocol adherence (90.6% vs 91.6%; p = 0.207), were similar between community and academic ICUs. CONCLUSIONS:. Community hospitals can conduct high-quality research, with similar trial metrics to academic hospitals. Patient characteristics differed between community and academic hospitals, highlighting the need for broader engagement of community hospitals in clinical research to ensure generalizability of study results.

This paper summarizes COVID-19 disease epidemiology in Canada in the pre-vaccine era—from January through to December 2020. Canadian case numbers, risk factors, disease presentations (including severe and critical disease), and outcomes are described. Differences between provinces and territories in geography, population size and density, health demographics, and pandemic impact are highlighted. Key concepts in public health response and mitigation are reviewed, including masking, physical distancing, hand washing, and the promotion of outdoor interactions. Adequate investment in public health infrastructure is stressed, and regional differences in screening and testing strategies are highlighted. The spread of COVID-19 in Canadian workplaces, long-term care homes, and schools is described and lessons learned emphasized. The impact of COVID-19 on vulnerable populations in Canada—including Indigenous Peoples, ethnic minorities and newcomers, people who use drugs, people who are homeless, people who are incarcerated, and people with disabilities—is described. Sex and gender disparities are also highlighted. Author recommendations include strategies to reduce transmission (such as test–trace–isolate), the establishment of nationally standardized definitions and public reporting, the protection of high risk and vulnerable populations, and the development of a national strategy on vaccine allocation.

Abstract Background Vancomycin-resistant enterococci (VRE) are a serious antimicrobial resistant threat in the healthcare setting. We assessed the cost-effectiveness of VRE screening and isolation for patients at high-risk for colonisation on a general medicine ward compared to no VRE screening and isolation from the healthcare payer perspective. Methods We developed a microsimulation model using local data and VRE literature, to simulate a 20-bed general medicine ward at a tertiary-care hospital with up to 1000 admissions, approximating 1 year. Primary outcomes were accrued over the patient’s lifetime, discounted at 1.5%, and included expected health outcomes (VRE colonisations, VRE infections, VRE-related bacteremia, and deaths subsequent to VRE infection), quality-adjusted life years (QALYs), healthcare costs, and incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analysis (PSA) and scenario analyses were conducted to assess parameter uncertainty. Results In our base-case analysis, VRE screening and isolation prevented six healthcare-associated VRE colonisations per 1000 admissions (6/1000), 0.6/1000 VRE-related infections, 0.2/1000 VRE-related bacteremia, and 0.1/1000 deaths subsequent to VRE infection. VRE screening and isolation accrued 0.0142 incremental QALYs at an incremental cost of $112, affording an ICER of $7850 per QALY. VRE screening and isolation practice was more likely to be cost-effective (> 50%) at a cost-effectiveness threshold of $50,000/QALY. Stochasticity (randomness) had a significant impact on the cost-effectiveness. Conclusion VRE screening and isolation can be cost-effective in majority of model simulations at commonly used cost-effectiveness thresholds, and is likely economically attractive in general medicine settings. Our findings strengthen the understanding of VRE prevention strategies and are of importance to hospital program planners and infection prevention and control.

Abstract Background Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality. Methods We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing. Results We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3 days (lower respiratory tract and gastric aspirates; interquartile range [IQR] 2–4) and 6 days (stool; IQR 4.25–6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r = − 0.46, p = 0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p = 0.045). Conclusions The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients. Trial registration ClinicalTrials.gov ID NCT01782755. Registered February 4 2013.

Background In Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection against vaccine-type IPD and pneumococcal community-acquired pneumonia (pCAP). Since vaccine recommendations in Canada include both age-based and risk-based guidance, this study aimed to describe the burden of vaccine-preventable pCAP in hospitalised adults by age.Methods Surveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed prospectively from 2010 to 2015. CAP was radiologically confirmed, and pCAP was identified using blood and sputum culture and urine antigen testing. Patient demographics and outcomes were stratified by age (16–49, 50–64, ≥65 and ≥50 years).Results Of 6666/8802 CAP cases tested, 830 (12.5%) had pCAP, and 418 (6.3%) were attributed to a PCV13 serotype. Of PCV13 pCAP, 41% and 74% were in adults aged ≥65 and ≥50 years, respectively. Compared with non-pCAP controls, pCAP cases aged ≥50 years were more likely to be admitted to intensive care units (ICUs) and to require mechanical ventilation. Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively.Conclusions Adults hospitalised with pCAP in the age cohort of 50–64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada.

Introduction Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysis The objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and dissemination Study approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration number NCT01782755; Pre-results.

We analyzed population-based surveillance data from the Toronto Invasive Bacterial Diseases Network to describe carbapenemase-producing Enterobacteriaceae (CPE) infections during 2007–2015 in south-central Ontario, Canada. We reviewed patients’ medical records and travel histories, analyzed microbiologic and clinical characteristics of CPE infections, and calculated incidence. Among 291 cases identified, New Delhi metallo-β-lactamase was the predominant carbapenemase (51%). The proportion of CPE-positive patients with prior admission to a hospital in Canada who had not received healthcare abroad or traveled to high-risk areas was 13% for patients with oxacillinase-48, 24% for patients with New Delhi metallo-β-lactamase, 55% for patients with Klebsiella pneumoniae carbapenemase, and 67% for patients with Verona integron-encoded metallo-β-lactamase. Incidence of CPE infection increased, reaching 0.33 cases/100,000 population in 2015. For a substantial proportion of patients, no healthcare abroad or high-risk travel could be established, suggesting CPE acquisition in Canada. Policy and practice changes are needed to mitigate nosocomial CPE transmission in hospitals in Canada.

Abstract Background The Serious Outcomes Surveillance (SOS) Network was established to monitor seasonal influenza complications among hospitalized Canadian adults and to assess the effectiveness of influenza vaccination against severe outcomes. Here we report age- and strain-specific vaccine effectiveness (VE) in preventing severe outcomes during a season characterized by mixed outbreaks of four different influenza strains. Methods This prospective, multicentre, test-negative case-control study evaluated the VE of trivalent influenza vaccine (TIV) in the prevention of laboratory-confirmed influenza-hospitalization in adults aged ≥16 years (all adults) and adults aged 16–64 years (younger adults). The SOS Network identified hospitalized patients with diagnoses potentially attributable to influenza during the 2011/12 influenza season. Swabs collected at admission were tested by reverse transcriptase polymerase chain reaction (RT PCR) or viral culture to discriminate influenza cases (positive) from controls (negative). VE was calculated as 1-odds ratio (OR) of vaccination in cases versus controls × 100. Results Overall, in all adults, the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 41.8% (95% Confidence Interval [CI]: 26.0, 54.3), and 42.8% (95% CI: 23.8, 57.0), respectively. In younger adults (16–64 years), the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 35.8% (95% CI: 4.5, 56.8) and 33.2% (95% CI: −6.7, 58.2), respectively. In the all adults group, adjusted VE against influenza A/H1N1 was 72.5% (95% CI: 30.5, 89.1), against A/H3N2 was 86.1% (95% CI: 40.1, 96.8), against B/Victoria was 40.5% (95% CI: −28.9, 72.6), and against B/Yamagata was 32.3% (95% CI: −8.3, 57.7). The adjusted estimate of early season VE (from November 1 to March 11) was 54.4% (95% CI: 29.7–70.4), which was higher than late season (from March 11 to May 25) VE estimate (VE: 29.7%, 95% CI: -5.3, 53.1). Conclusions These results suggest that TIV was highly effective against A viruses and moderately effective against B viruses during a mild season characterised by co-circulation of four influenza strains in Canada. Findings underscore the need to provide VE assessment by subtype/lineage as well as the timing of vaccination (early season vs late season) to accurately evaluate vaccine performance and thus guide public health decision-making. Trial registration ClinicalTrials.gov Identifier: NCT01517191. Registration was retrospective and the date of registration was January 17, 2012.

OBJECTIVE:Many jurisdictions lack comprehensive population-based antibiotic use data and rely on third party companies, most commonly IQVIA. Our objective was to validate the accuracy of the IQVIA Xponent antibiotic database in identifying high prescribing physicians compared to the reference standard of a highly accurate population-wide database of outpatient antimicrobial dispensing for patients ≥65 years. METHODS:We conducted this study between 1 March 2016 and 28 February 2017 in Ontario, Canada. We evaluated the agreement and correlation between the databases using kappa statistics and Bland-Altman plots. We also assessed performance characteristics for Xponent to accurately identify high prescribing physicians with sensitivity, specificity, positive predictive value (PPV), and negative predictive value. RESULTS:We included 9,272 physicians. The Xponent database has a specificity of 92.4% (95%CI 92.0%-92.8%) and PPV of 77.2% (95%CI 76.0%-78.4%) for correctly identifying the top 25th percentile of physicians by antibiotic volume. In the sensitivity analysis, 94% of the top 25th percentile physicians in Xponent were within the top 40th percentile in the reference database. The mean number of antibiotic prescriptions per physician were similar with a relative difference of -0.4% and 2.7% for female and male patients, respectively. The error was greater in rural areas with a relative difference of -8.4% and -5.6% per physician for female and male patients, respectively. The weighted kappa for quartile agreement was 0.68 (95%CI 0.67-0.69). CONCLUSION:We validated the IQVIA Xponent antibiotic database to identify high prescribing physicians for patients ≥65 years, and identified some important limitations. Collecting accurate population-based antibiotic use data will remain vital to global antimicrobial stewardship efforts.

Contaminated surfaces serve as an important reservoir for Clostridium difficile transmission. Current strategies to detect environmental contamination of C. difficile rely heavily on culture, and often only indicate presence versus absence of spores. The goal of this study was to compare quantitative PCR (qPCR) to culture for the detection and quantification of C. difficile from inert surfaces. First, we compared the limit of detection (LOD) of a 16S rRNA gene and toxin B gene qPCR assay for detection of C. difficile in solution. Second, we compared the LODs of 16S rRNA gene qPCR versus culture for detection of C. difficile from surfaces. Solution experiments were performed by direct seeding of spores into neutralizing broth, whereas surface experiments involved seeding of spores onto plastic test surfaces, and recovery using sponge swabs. Both experiments were conducted using spores expressing short (NAP1) and long (NAP4) hair lengths. Combining data from both strains, the overall LOD for C. difficile cells in solution was 1.4 cells for 16S rRNA gene and 23.6 cells for toxin B gene qPCR (p

The objective of this study was to describe the epidemiology, clinical characteristics, microbiology and outcomes of patients of all ages with Streptococcus pneumoniae meningitis between 2000 and 2004; two years pre- and postintroduction of an S pneumoniae 7-valent conjugate vaccine program in Alberta in children younger than two years of age. The high mortality rate associated with S pneumoniae meningitis, despite appropriate therapy, suggests that prevention of S pneumoniae meningitis is critical. Despite implementation of a PCV-7 program in Alberta, rates of S pneumoniae meningitis in children younger than two years of age is still high. Thus, continued research into safe and efficacious vaccines covering a broader range of S pneumoniae serotypes is necessary.

To determine if immune phenotypes associated with immunosenescence predict risk of respiratory viral infection in elderly nursing home residents.Residents ≥ 65 years from 32 nursing homes in 4 Canadian cities were enrolled in Fall 2009, 2010 and 2011, and followed for one influenza season. Following influenza vaccination, peripheral blood mononuclear cells (PBMCs) were obtained and analysed by flow cytometry for T-regs, CD4+ and CD8+ T-cell subsets (CCR7+CD45RA+, CCR7-CD45RA+ and CD28-CD57+) and CMV-reactive CD4+ and CD8+ T-cells. Nasopharyngeal swabs were obtained and tested for viruses in symptomatic residents. A Cox proportional hazards model adjusted for age, sex and frailty, determined the relationship between immune phenotypes and time to viral infection.1072 residents were enrolled; median age 86 years and 72% female. 269 swabs were obtained, 87 were positive for virus: influenza (24%), RSV (14%), coronavirus (32%), rhinovirus (17%), human metapneumovirus (9%) and parainfluenza (5%). In multivariable analysis, high T-reg% (HR 0.41, 95% CI 0.20-0.81) and high CMV-reactive CD4+ T-cell% (HR 1.69, 95% CI 1.03-2.78) were predictive of respiratory viral infection.In elderly nursing home residents, high CMV-reactive CD4+ T-cells were associated with an increased risk and high T-regs were associated with a reduced risk of respiratory viral infection.

Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases.The advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX3CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.These data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation.

BACKGROUND: Little is known about risk factors for severe outcomes in patients infected with H5N1 and no systematic review has been conducted. Understanding risk factors is an important step for prioritizing prophylaxis or treatment in the event of a pandemic. OBJECTIVES: To systematically evaluate risk factors for severe outcomes in patients with avian influenza H5N1 infection. DATA SOURCES: MEDLINE, EMBASE, CINAHL, GlobalHealth, and CENTRAL through March 2011. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies of any design published in English, French, Spanish, German or Korean that reported on risk factor-outcome combinations of interest in participants with confirmed H5N1 infections. Outcomes considered included death, ventilator support, hospital and ICU admission, pneumonia, and composite outcomes. STUDY APPRAISAL: Risk of bias was assessed using the Newcastle-Ottawa scale (NOS). RESULTS: We identified 20 studies reporting on 999 patients infected with H5N1. The majority of studies (n = 14, 70%) were at intermediate risk of bias, i.e. 4-6 points on the NOS. Females were at increased risk of death (OR 1.75, 95% CI 1.27-2.44), while young age, in particular